1. b Chapter 11~ Cell Communication

2. Signal-transduction pathway I b Def: Process by which a signal on a cell’s surface is converted into a specific cellular response b Local signaling (short distance): Messenger moleucles are secreted and travel short distancesMessenger moleucles are secreted and travel short distances Paracrine signaling (growth factors)Paracrine signaling (growth factors) –Single cell produces factors that are received and responded to by numerous cells simultaneously Synaptic (neurotransmitters)Synaptic (neurotransmitters) –Electrical signal stimlates secretion of chem signal which moves across the synapse to another cell

3. Signal-transduction pathway II b Long distance: hormones Animals - aka endocrine signalingAnimals - aka endocrine signaling –Hormones released into circulatory system to travel to target cells –Nervous system – signal continues along a series of cells Plants – growth regulatorsPlants – growth regulators –Travel by vessels, diffusion through cells, or the air as a gas

4. Stages of cell signaling b Discovered by Earl Sutherland (‘71) Glycogen depolymerization by epinephrineGlycogen depolymerization by epinephrine b 3 steps: b (1) Reception: target cell detection b (2) Transduction: single-step or series of changes b (3) Response: triggering of a specific cellular response

5. Reception I b A signal molecule binds to a receptor protein and causes a conformation change b Ligand – molecule that specifically binds to another b Compare to a key in a lock – similar to enzymes b Intracellular receptors Proteins found in cytoplasm or nucleus of target cellProteins found in cytoplasm or nucleus of target cell Messenger must pass through plasma membraneMessenger must pass through plasma membrane Must be hydrophobic or small enoughMust be hydrophobic or small enough Ex. Steroids, thyroid hormonesEx. Steroids, thyroid hormones Testosterone – released by testisTestosterone – released by testis –Target cells have receptor in nucleus –Binds w/ protein activating it –Active form enters nucleus and turns on specific genes

6. Reception II b Plasma membrane receptors (pg 206-208) Water soluble signal moleculesWater soluble signal molecules Receptor transmits info by changing shapeReceptor transmits info by changing shape 3 main types3 main types (1) G-protein-linked receptors(1) G-protein-linked receptors –Receptor is made of 7 transmembrane α helices –Works w/ the help of a G protein which is just inside the membrane –Is on or off depending on which of 2 guanine nucleotides is attached (GDP or GTP) –Signal molecule binds to receptor and changes its shape –Binds to GDP causes GTP to replace it –GTP binds to an enzyme and activates it –Reverts to GDP

7. Reception III (2) Receptor Tyrosine Kinases(2) Receptor Tyrosine Kinases –Can trigger simultaneous signal transduction pathways –Regulates cell growth and reproduction –Malfunction may lead to cancer –Kinase – enzyme catalyzes phosphate transfers in cytoplasm –Portion of receptor acts as a tyrosine kinase –Signal molecule causes 2 receptors to move close together (dimerization) –Activates tyrosine kinase –Attaches phosphates to tyrosines –Different inactive proteins bind to phosphorylated tyrosine and become activated

8. Reception IV (3) Ligand-gated ion channels(3) Ligand-gated ion channels –Important for nervous system –When receptor changes shape a “gate” opens/closes allowing ions through or blocking flow –Cause changes in Na+ and Ca- concentration levels

9. Transduction I b Series (cascade) of molecular interactions relay signals from receptors to target molecules b Begins when receptor changes b Relay molecules = proteins b @ each step info is transduced into a different form Usually a conformation change in proteinUsually a conformation change in protein Caused by phosphorylationCaused by phosphorylation

10. Transduction II Protein kinase – enzyme that transfers a phosphate from ATP to protein – many different kindsProtein kinase – enzyme that transfers a phosphate from ATP to protein – many different kinds Addition of phosphate activates proteinAddition of phosphate activates protein b Dephosphorylation – removal of phosphate Inactivates proteins – turn off pathwayInactivates proteins – turn off pathway Caused by enzymes called protein phosphatasesCaused by enzymes called protein phosphatases

11. Second Messengers I b Small molecules and ions that are not proteins b 1 st is the extracellular signal molecule that binds to membrane b Are able to diffuse through cells b 2 most common:cyclic AMP &calcium ions

12. Second Messengers II b (1) cyclic AMP (cAMP) Adenylyl cyclase (enzyme in membrane) converts ATP to cAMPAdenylyl cyclase (enzyme in membrane) converts ATP to cAMP Concen. increases and spreads through cellConcen. increases and spreads through cell Only lasts while signal molecule is attachedOnly lasts while signal molecule is attached Concen. decreases because phosphodiesterase changes cAMP back to ATPConcen. decreases because phosphodiesterase changes cAMP back to ATP

13. Second Messengers III b (2)Calcium ions and Inositol Triphosphate (IP3) Ca concen. increases triggered by other secondary messengersCa concen. increases triggered by other secondary messengers Phospholipid in membrane is broken into IP3 and diaglycerol (DAG)Phospholipid in membrane is broken into IP3 and diaglycerol (DAG) IP3 goes on to stimulate Ca increaseIP3 goes on to stimulate Ca increase

14. Response b Regulation of cellular activities b In cytoplasm b Ex. Open/close ion channel; change in metabolism b May cause synthesis of enzymes

15. Specificity of Cell Signaling b Get different results from different cells because they have different collections of proteins b Ex. Epinephrine – a liver cell breaks down glycogen; heart cells contract for faster heart beat

16. Signaling Efficiency b Scaffolding proteins – large relay proteins w/ other relay proteins attached b Increases efficiency